β2 Glycoprotein 1 Antibodies

Recently, an international consensus group of experts in the diagnosis and management of antiphospholipid syndrome (APS) concluded that β2-glycoprotein 1 (β2-GP 1) IgG and IgM antibodies should be included as diagnostic criteria for APS.1 This group determined that the presence of one or both of these antibodies is an independent risk factor for thrombosis and pregnancy complications.1

The term “antiphospholipid” does not fully describe the target of anticardiolipin antibody assays. A common aspect to all assays for anticardiolipin antibodies is the requirement that the assay system include a source of plasma proteins.2 In many cases, antiphospholipid antibodies require the presence of specific proteins to facilitate phospholipid binding.3-5 It has been determined that, in many patients, the required plasma factor is β2-glycoprotein 1 (β2-GP 1)2,5,6 Solid phase enzyme immunoassays that detect antibodies that bind to β2-GP 1 in the absence of phospholipid are now part of the diagnostic arsenal for APS.

  • β2-GP 1-dependent antibody binding is frequently detected in patients with clinical symptoms of APS.2
  • Anticardiolipin antibodies associated with infections do not tend to be β2-GP 1-dependent.2This supports the conclusion that anti-β2-GP 1 assays may be more specific for APS than anticardiolipin antibodies.2,5-7
  • While the majority of patients with lupus anticoagulants will also test positive for anticardiolipin antibodies and/or β2-GP 1 antibodies, approximately 30% of patients tested will have discordant results.3,4
  • Approximately 20% of patients that test negative for anticardiolipin antibodies will test positive for β2-GP 1.3
  • Positive anti-β2-GP 1 results tend to support the diagnosis of APS in patients with a strong clinical picture for APS with negative lupus anticoagulants and anticardiolipin antibody results.7
  • Anti-β2-GP 1 testing can be useful in the evaluation of patients with positive anticardiolipin antibody results and a clinical picture that is not consistent with APS.2,6,7 A negative anti-β2-GP 1 result in this context would not support a diagnosis of APS.

References

1. Miyakis S, Lockshin MD, Atsumi T, et al. International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome (APS). J Thromb Haemost. 2006 Feb; 4(2):295-306.PubMed 16420554

2. Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome? J Autoimmun. 2000 Sep; 15(2):163-172. PubMed 10968904

3. Triplett DA. Coagulation abnormalities. In McClatchey KD, ed. Clinical Laboratory Medicine. 2nd ed. Baltimore, Md: Lippincott Williams and Wilkins; 2002:1033-1049.

4. Hirsh J, Anand SS, Halperin JL, Fuster V; American Heart Association. Guide to anticoagulant therapy. Heparin: A statement for healthcare professionals from the American Heart Association. Circulation. 2001 Jun 19; 103(24):2994-3018.PubMed 11413093

5. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. 2002 Mar 7, 346(10):752-763. PubMed 11882732

6. Reddel SW, Krilis SA. Testing for and clinical significance of anticardiolipin antibodies. Clin Diagn Lab Immunol. 1999 Nov; 6(6):775-782.PubMed 10548562

7. Harris EN, Pierangeli SS, Gharavi AE. Diagnosis of the antiphospholipid syndrome: A proposal for use of laboratory tests. Lupus. 1998; 7(Suppl 2):S144-S148. PubMed 9814693

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